Abstract
Brain tumors are among the deadliest malignancies. The brain tumor microenvironment (TME) hosts a unique collection of cells, soluble factors, and extracellular matrix components that regulate disease evolution of both primary and metastatic brain malignancies. It is established that macrophages and other myeloid cells are abundant in the brain TME and strongly correlate with aggressive phenotypes and distinct genetic signatures, while lymphoid cells are less frequent but are now known to have a pronounced effect on disease progression. Different types of brain tumors vary widely in their microenvironmental contexture, and the proportion of various stromal components impacts tumor biology. Indeed, emerging evidence suggests an intimate link between the molecular signature of tumor cells and the composition of the TME, shedding light on the mechanisms which underlie microenvironmental heterogeneity in brain cancer. In this review, we discuss the association between TME composition and the diverse molecular profiles of primary gliomas and brain metastases. We also discuss the implications of these associations on the efficacy of immunotherapy in brain malignancies. An appreciation for the causes and functional consequences of microenvironmental heterogeneity in brain cancer will be of crucial importance to the rational design of microenvironment-targeted therapies for these deadly diseases.
Highlights
The clinical management of brain tumors remains a significant challenge, as surgery and standard of care (SOC) cytotoxic therapies often offer minimal survival benefit
The brain hosts a generally immunosuppressive milieu that protects the delicate and non-regenerative neural tissue from inflammatory insult. This is in part regulated by the blood-brain barrier (BBB), a selectively permeable barrier formed by endothelial cells, pericytes, and astrocytes [1, 2], which shields the brain from toxins, pathogens, and inflammatory cells within the peripheral circulation
The work we present focuses primarily on gliomas and brain metastases, but we include examples drawn from studies on pediatric and rare neurological tumors in order to provide a more complete picture of tumor microenvironment (TME) heterogeneity in brain cancer
Summary
Reviewed by: Catherine Sautes-Fridman, INSERM U1138 Centre de Recherche des Cordeliers, France David George Menter, University of Texas MD Anderson Cancer Center, United States. Brain tumors are among the deadliest malignancies. The brain tumor microenvironment (TME) hosts a unique collection of cells, soluble factors, and extracellular matrix components that regulate disease evolution of both primary and metastatic brain malignancies. Emerging evidence suggests an intimate link between the molecular signature of tumor cells and the composition of the TME, shedding light on the mechanisms which underlie microenvironmental heterogeneity in brain cancer. We discuss the association between TME composition and the diverse molecular profiles of primary gliomas and brain metastases. We discuss the implications of these associations on the efficacy of immunotherapy in brain malignancies. An appreciation for the causes and functional consequences of microenvironmental heterogeneity in brain cancer will be of crucial importance to the rational design of microenvironment-targeted therapies for these deadly diseases
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